AB0177 ESTIMATING CAUSALITY FOR POLYARTERITIS NODOSA WITH IL-1, AND IL-10: MENDELIAN RANDOMISATION ANALYSES
Authors: Y. Zhang, R. Zhao, H. Zhang, Y. Hou, S. X. Zhang, X. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Polyarteritis nodosa (PAN) is a primary form of vasculitis characterized by inflammation of primarily medium-sized arteries[1]. Although the etiology of vasculitis is not fully understood, it has been suggested that cytokines(including interleukin-1 (IL-1) and interleukin-10(IL-10)) are significantly associated with a high susceptibility to vasculitis[2, 3]. However, there is no relevant research to explore the causality and direction of this association between interleukin and PAN. <h3>Objectives</h3> In this study, we intended to detect the casual association between PAN and interleukin using two-sample Mendelian randomization (MR) analysis. <h3>Methods</h3> The summary statistics of PAN were obtained from the FinnGen consortium release data (82 cases and 213145 controls). We also selected genetic instruments associated with il-1 and il-10 from the study of Sun et al. (3301 sample size). Initially, SNPs associated with interleukin at the genome-wide significance threshold (p&lt;1×10<sup>-5</sup>) were extracted. Afterwards, We used a two-sample mendelian randomization analysis to explore the causal associations between PAN with IL-1, and IL-10. The inverse variance weighted (IVW) was the primary approach to calculating the effect estimates. To increase the IVW estimates, we also used other MR methods, such as MR-Egger and weighted median. Additionally, Sensitivity analyses of evaluating the influence of outliers and pleiotropy effects were performed by a variety of MR methods. All Statistical analyses were performed using R (version 4.2.1). <h3>Results</h3> Using single-nucleotide polymorphisms (SNPs) of genome-wide significance as instrumental variables, we did not find a significant association of IL-1α(odds ratio[OR] = 1.044, 95% confidence interval [CI]: 0.551 to 1.981, p = 0.895), IL-1β (odds ratio[OR] = 0.986, 95% confidence interval [CI]: 0.557 to 1.745, p = 0.962), and IL-10 (odds ratio[OR] = 1.066, 95% confidence interval [CI]: 0.621 to 1.832, p = 0.815) on PAN. Likewise, Comparable results were obtained using MR-Egger regression, and weighted median. We did not find evidence to support a causal association between IL-1α, IL-1β, IL-10, and PAN. <h3>Conclusion</h3> The results of this study based on genetic data did not support a causal relationship between PAN and Il-1, IL-10. <h3>References</h3> [1]Saadoun D, Vautier M, Cacoub P. Medium- and Large-Vessel Vasculitis. Circulation. 2021;143(3):267-82. [2]Cavalli G, Colafrancesco S, Emmi G, Imazio M, Lopalco G, Maggio MC, et al. Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2021;20(3):102763. [3]Lee PY, Day-Lewis M, Henderson LA, Friedman KG, Lo J, Roberts JE, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020;130(11):5942-50. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.